Biochemical changes of connective tissue macromolecules of cardiovascular structures are important in the pathogenesis of cardiovascular diseases. This research program is involved in developing methods for the study of connective tissue macromolecules of cardiovascular structures and attempting to understand better the involvement of connective tissue components in the pathogenesis of atherosclerosis. Since the characterization of glycosaminoglycans (GAG) from the arterial wall is mostly completed, attention is now directed to the nature of proteoglycans and interaction of the carbohydrate macromolecules with fibrous structures and serum lipoproteins being transported through the arterial wall. A proteoglycan containing chondroitin sulfate and dermatan sulfate has been characterized. Another proteoglycan which contains primarily heparan sulfate, 15% protein, 19% uronic acid, 20% hexosamine as glucosamine with a sulfate to hexosamine ratio of 0.76 has been isolated; an estimated molecular weight of 60,000 to 70,000 was determined. Enzymatic studies suggest this proteoglycan is tightly associated with elastin in the arterial wall. Further studies on the interaction of arterial GAG and serum lipoproteins (LP) indicate by electron microscopy that LP-GAG complexes from fibrous plaque extracts assume the particle size of 1000 - 2000 A. The particles are spherical and electron transparent. Serum VLDL and LDL complex in vitro with GAG and both assume a similar configuration and morphology. Similar configurations were obtained with complexes from the arterial wall. These studies indicate an interaction of GAG with LP and suggest an important role of GAG in the pathogenesis of atherosclerotic lesions. Further studies are in progress with other investigators to characterize connective tissue macromolecules from tissues being supplied from studies of experimental atherosclerosis in nonhuman primates. These investigations explore induction and regression of experimental lesions and stimulate human atherosclerosis. BIBLIOGRAPHIC REFERENCE: Dalferes, E.R., Jr., Radhakrishnamurthy, B., Crouch, M.S. and Berenson, G.S.: A study of connective tissue macromolecules in skin of mice with goldthioglucose-induced obesity. Proc. Soc. for Exper. Biol. and Med., 148:918, 1975.